PCI-34051

PCI-34051 is a potent and selective HDAC8 inhibitor with IC₅₀ of 10 nM, with >200-fold selectivity over the other HDAC isoforms. IC50 & Target: IC50: 10 nM (HDAC8), 2.9 μM (HDAC6), 4 μM (HDAC1), 13 μM (HDAC10)^[1] In Vitro: PCI-34051 inhibits pure recombinant HDAC8 with K_i of 10 nM with >200-fold selectivity over the other HDACs tested, including HDACs 1, 2, 3, 6 and 10. PCI-34051 is derived from a low molecular weight hydroxamic acid scaffold that possessed promising potency (HDAC8; K_i=2 μM) and selectivity (approximately fivefold) for HDAC8 relative to the other class I HDACs. PCI-34051 is found to induce apoptosis at low micromolar concentrations in cell lines derived from T-cell lymphomas, including Jurkat and HuT78, whereas doses as high as 20 μM has no effect on B-cell- or myeloid-derived lymphomas or solid tumor lines^[1]. In Vivo: Administration of PCI-34051 and Dexamethasone reduces the eosinophilic inflammation and airway hyperresponsiveness in asthma to reduce the airway remodeling^[2].